Rapid reversal of digitalis delirium using digoxin immune fab therapy

A fulminant psychiatric disturbance, as the sole noncardiac manifestation of digitalis toxicity, emerged in a 85-year-old woman during treatment for congestive heart failure. Described more than a century ago as ‘digitalis delirium,’ the disorder is characterized by severe agitation, delusional thinking, assaultive behavior, and even death. Digoxin immune Fab therapy was begun because of the fulminant psychiatric manifestations of this toxic state and the clear danger of self-inflicted physical harm. Within 3 h of therapy, a complete and spectacular resolution of all mental symptoms was observed.     

First clinical experiences with specific sheep Fab fragments in snake bite. Report of a multicentre study of Vipera berus envenoming

Objectives. To evaluate the efficacy and safety of specific, ovine Fab fragments in the treatment of envenoming by the common adder, Vipera berus.
Design. Open study with historical controls.
Setting. Multicentre study involving patients ( n = 30) with V. berus envenoming, treated in 18 Swedish hospitals during 1991–94.
Main outcome measures. Initial symptoms, clinical course after treatment, duration of hospital stay and adverse effects of the antivenom were evaluated. Two earlier studied patient groups, given either equine F(ab')₂ antivenom ( n = 30) or no antivenom ( n = 16), were used as controls.
Results. Specific ovine Fab fragments influenced favourably the acute symptomatology as well as the long term clinical course. Acute symptoms such as hypotension, shock, vomiting, diarrhoea and CNS-depression resolved quickly. The incidence of extensive swelling involving the trunk and the length of hospital stay were both reduced significantly compared to nontreated patients (23 vs. 88% and 3.5 vs. 6 days). Also the incidence of anaemia was reduced (23 vs. 44%). These results were consistent with those obtained with equine F(ab')₂ antivenom, but with ovine Fab there were no immediate anaphylactic reactions or serum sickness.
Conclusion. Specific Fab fragments produced from sheep immunized with V. berus venom were safe and effective in counteracting the effects of V. berus bite in humans. These results justify further studies of this new treatment for snake envenoming.     

The impact of serum concentration-guided digoxin therapy on mortality of heart failure patients: A long-term follow-up,propensity-matched cohort study

BackgroundRecently published studies suggested that digoxin may increase mortality in heart failure with reduced ejection fraction (HFrEF). However, in the vast majority of former trials serum digoxin concentration (SDC) was not measured and therapy was not SDC‐guided.AimTo assess the impact of SDC‐guided digoxin therapy on mortality in HFrEF patients.MethodsData of 580 HFrEF patients were retrospectively analyzed. In patients on digoxin, SDC was measured every 3 months and digoxin dosage was SDC‐guided (target SDC: 0.5‐0.9 ng/mL). All‐cause mortality of digoxin users and nonusers was compared after propensity score matching (PSM).ResultsAfter 7.1 ± 4.7 years follow‐up period (FUP) all‐cause mortality of digoxin users (n = 180) was significantly higher than nonusers (n = 297) (propensity‐adjusted HR = 1.430; 95% CI = 1.134‐1.804; P = .003). Patients having SDC of 0.9 to 1.1 ng/mL (n = 60) or > 1.1 ng/mL (n = 44) at any time during the FUP had an increased risk of all‐cause mortality (HR = 1.750; 95% CI = 1.257‐2.436, P = .001 and HR = 1.687; 95% CI = 1.153‐2.466, P = .007), while patients having a maximal SDC < 0.9 ng/mL (n = 76) had similar mortality risk (HR = 1.139; 95% CI = 0.827‐1.570, P = .426), compared to digoxin nonusers.ConclusionsAccording to our propensity‐matched analysis, SDC‐guided digoxin therapy was associated with increased all‐cause mortality in optimally treated HFrEF patients, especially with SDC ≥0.9 ng/mL. These results reinforce the expert opinion that digoxin in HFrEF can only be used among carefully selected patients with close SDC monitoring.     

Improved control of atrial fibrillation with combined pindolol and digoxin therapy

This study has compared the effect on heart rate control of the addition of pindolol 15 mg bd or verapamil 40 mg tds to maintenance digoxin therapy in 12 patients with chronic atrial fibrillation. The study was performed in a randomized cross-over fashion. Treatment effects were assessed by 24-h ambulatory electrocardiography and symptomatic improvement by symptom scores. The results show that the combination of pindolol and digoxin provides better control of atrial fibrillation. With an attenuation of daytime tachycardia, prevention of nocturnal bradycardia and reduction in the length of nocturnal pauses in rhythm. Overall heart rate variability was significantly less with digoxin and pindolol (523 beats min-1 h-1) than with digoxin and verapamil (745 beats min-1 h-1). We conclude that, in the dosages employed, combined digoxin and pindolol therapy is superior to either digoxin and verapamil in combination or digoxin alone for the treatment of atrial fibrillation.     

Increasing US mortality due to accidental poisoning: the role of the baby boom cohort

Aims In this study we examine whether the recent, sharp increase in mortality in the United States due to accidental poisoning since 2000 is the result of the aging of the baby boom cohort or, instead, a historical trend apparent among decedents of all ages. Design We conducted an age–period–cohort analysis using data from the US Vital Statistics and the US Census covering the period 1968–2007. Setting and participants The United States population aged 15–64 years. Measurements Cause of death and demographic data as recorded on death certificates. Findings The increase in mortality due to accidental poisoning since the year 2000 stems primarily from a historical period effect across all ages for whites, but results in large part from a rate spike in the baby boom cohort among blacks. For all demographic groups baby boomers had higher odds of death due to accidental poisoning than the cohorts that came before and after them. Historical influences acting across all ages led to an increase in accidental poisoning mortality that was almost 10‐fold for whites and threefold for blacks over the study period. Conclusions While the recent, sharp increase in accidental poisoning mortality stems in part from the aging of the baby boom cohort, substantially more of the increase results from influences unique to recent years that have affected all age groups. These results point to the need to bolster overdose prevention programs and policies as the historical increase in accidental poisoning mortality appears to continue unabated.     

Hemodynamic effects of intravenous prenalterol in patients on long-term digoxin therapy for congestive heart failure

The hemodynamic effects of a new beta-1-adrenoceptor agonist,prenalterol, were studied in 12 patients with regurgitant valvedisease and/or ischemic heart disease (prenalterol group). Fiveother patients were randomized to a control group and studiedin the same way except that saline was administered insteadof prenalterol. All patients were on long-term digoxin therapy.Heart rate, stroke volume, cardiac output, arteriovenous oxygendifference, pressures in the right atrium, pulmonary arteryand left ventricle were determined both at rest and during recumbentexercise before and after administration of 50 µg prenalterol/kgbody weight, or of saline. Prenalterol caused a significant increase in heart rate andcardiac output and a significant reduction in arteriovenousoxygen difference, in left ventricular filling pressure andin right atrial pressure both at rest and during exercise. Asignificant increase of stroke volume was seen only during exercise.In the placebo group, no significant hemodynamic changes wererecorded. No adverse effects were observed. Thus, prenalterol seems to have beneficial hemodynamic effects,additive to those of digitalis. The drug is potentially usefulin the treatment of heart failure, but further studies on thespecific mechanism of action and the long-term effects are warranted.     

A comparison of verapamil and digoxin in the treatment of atrial fibrillation

Twelve patients (including 2 females) with chronic atrial fibrillationwere entered into a randomized, double blind crossover studyto compare the effects of digoxin and verapamil upon heart rate,exercise tolerance and symptom control. The dose of digoxinwas adjusted so as to give serum concentrations within the range1.3 to 2.6 nmol ^l–1 between four and six hours after dosing,and was continued for six weeks. The dose of verapamil was increasedfrom 40 mg tds to 80 mg tds to 120 mg tds at fortnightly intervals.Three patients did not complete the study; two because of adverseeffects attributable to verapamil. In the remaining nine patients,mean post exercise heart rates were significantly lower duringtreatment with verapamil 80 mgs tds (126.7bpm) than with verapamil40 mg tds (148.6 bpm) or digoxin (146.7 bpm). However, exercisetolerance was similar with both verapamil and digoxin and thesuperior control of exercise induced tachycardia achieved withhigher doses of verapamil was not associated with improved exerciseendurance. Visual analogue scale scores for constipation weresignificantly higher during treatment with verapamil; scoresfor other possible side effects and for overall wellbeing weresimilar. The results do not confirm the findings of others whohave reported that verapamil is superior to digoxin in the treatmentof atrial fibrillation.     

The captopril-digoxin multicenter resarch group study on the comparative steps of captopril and digoxin in patients with mildmoderate heart failure: Implications for therapy

Summary It is argued that the basis of therapy in a patient with mild-to-moderate congestive heart failure should be a combination of a diuretic and a converting enzyme inhibitor, with the further addition of digoxin if necessary.     

Reassessment of digoxin and other low-dose positive inotropes in the treatment of chronic heart failure

Summary Digoxin and other low doses of drugs that have inotropic properties may have an important role to play in the therapy of patients with chronic heart failure. There is convincing evidence that digoxin is effective in relieving the signs and symptoms of heart failure due to systolic dysfunction. While earlier results with some of the other agents have been disappointing, recent data suggest that a reevaluation of these agents is necessary. There is now compelling evidence that lower doses of these agents may be clinically useful without necessarily having any significant hemodynamic effects. The recent experience with vesnarinone is especially promising in showing that therapy with these agents may improve survival in addition to improving clinical status. It is becoming recognized that hemodynamic activity should not necessarily be a prerequisite for clinical utility for these agents. The neuroendocrine and electrophysiologic effects of many of these agents, including digitalis, remain incompletely characterized and may play an important role in their therapeutic benefit. It appears that certain drugs that have inotropic properties may be effective only when their inotropic effects are not readily demonstrated. Further research into the appropriate mechanisms of action and proper dosing of these drugs may lead to a renewed interest in the use of positive inotropes for chronic heart failure.     

Does digoxin have a place in the treatment of the child with congenital heart disease?

Summary The place of digoxin in the pediatric cardiologist's armamentarium remains uncertain. As an antiarrhythmic, its use in the Wolff-Parkinson-White syndrome is obsolete, but it remains useful in the treatment of the chronic atrial fibrillation seen in some patients postoperatively and in children with dilated cardiomyopathy. The efficacy of digoxin in heart failure is unproven. There is some evidence of improvement in non invasive left ventricular contractile indices in neonates and infants, but it is unclear whether this is associated with sustained clinical improvement. There is even less evidence of its effectiveness in the older child. Whilst the measurement of any effect will undoubtedly be difficult, the time has come for double-blind, placebo-controlled trials in selected groups of patients. These should be designed not only to test the notion that digoxin does not improve ventricular function, but also to embrace the possibility that its administration may result in clinical improvement over and above that following diuretics alone. An absence of proof of efficacy must be distinguished from no efficacy—more data are needed.JSC is supported by the Hyman Marks Pediatric Research Fund.     

Profibrillatory effects of verapamil but not of digoxin in the goat model of atrial fibrillation

INTRODUCTION: Verapamil and digoxin have been shown to modulate tachycardia-induced atrial electrical remodeling. The goal of the present study was to determine the direct effects of verapamil and digoxin on atrial fibrillation (AF), before and after electrical remodeling. METHODS AND RESULTS: In six goats we measured the AF cycle length (AFCL) and duration of AF (DurAF) of 50 consecutive induced paroxysms, before (t = 0) and after 24 hours (t = 24) of electrical remodeling. During AF, conduction velocity (CV(AF)), refractory period (RP(AF)), and type of AF (I, II, III) were determined. Verapamil was administered at a loading dose of 0.1 mg/kg, followed by a continuous (2-hour) infusion of 5 microg/kg/min. Digoxin was given intravenously as a single 0.02 mg/kg bolus. At t = 0 and t = 24, digoxin and verapamil caused a significant slowing of the ventricular rate of >40%. Digoxin had no effect on DurAF, AFCL, CV(AF), or RP(AF). Infusion of verapamil had a direct proarrhythmic effect. Both at t = 0 and t = 24, AFCL and RP(AF) were shortened by about 15%. During acute AF, verapamil prolonged the average duration of AF paroxysms from 7 to 16 seconds. After 24 hours of AF, the proarrhythmic effect was much stronger. Shortly after starting infusion (6 +/- 2 min), verapamil converted paroxysmal AF into sustained AF. As long as verapamil infusion was maintained, AF no longer terminated in any of the goats. This effect was associated with an increase in AF fragmentation from type I to type II-III. CONCLUSION: Verapamil shortens AFCL and RP(AF) in the presence and absence of electrical remodeling. After 24 hours, it exerted a marked proarrhythmic effect and converted paroxysmal (type I) into sustained (type III) AF. In contrast, digoxin had no effect on the rate or stability of AF.